DESCRIPTION: Alzheimer's disease (AD), is a major health problem in the United States, where it affects approximately four million older individuals. There is no effective treatment of AD and prevention is the key to this disorder. Oxidative stress, in the form of lipid, protein, carbohydrate and DNA oxidation plays a significant role in the pathogenesis of neuron degeneration in AD and serves as a potential therapeutic target for slowing the onset or preventing the disease. The present application, termed PREADVISE, is based on the hypothesis that early treatment with vitamin E and selenium (Se) in the presymptomatic stage of the disease may delay the onset or prevent AD. These two agents have strong antioxidant properties and have not been used together in a large human study. This proposed evaluation of AD prevention will be added to the Selenium and Vitamin E Chemoprevention Trial (SELECT), a NCI-supported, phase III, double-blind, placebo-controlled 2X2 factorial study that assesses the combined and single effect of these two antioxidants on the reduction of the incidence of prostate cancer in 32,400 healthy men 55 or older (50 or older if African American). The duration of SELECT will be 12 years with a five-year uniform accrual period. PREADVISE is open to men 65 or older (60 or older if a minority) and it is estimated that 10,368 participants will be enrolled. They will be randomized to one of four arms: vitamin E plus Se, vitamin E plus Se placebo, Se plus vitamin E placebo, or vitamin E and Se placebos. They will undergo a memory impairment screening examination as part of the initial and annual SELECT evaluation, and those that fall below the cutoff point will undergo a more thorough cognitive evaluation using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Participants who fail the CERAD battery will receive a thorough dementia medical evaluation for diagnosis and be reviewed in a consensus conference by neurologists and a neuropsychologist with lengthy experience in dementia. It is estimated that the relative risk for AD (relative risk 0.60) is detectable with 80 percent power in this trial. The study offers an inexpensive opportunity to evaluate the long-term effect of two antioxidant agents in slowing the onset or preventing AD in a large number of subjects. The study also will evaluate the sensitivity and specificity of the screening measure in a matched sample of normals. In addition, it will evaluate the effect of antioxidant therapy in a group of 200 elderly longitudinally followed normal controls.